Antigen-specific T suppressor cells have been identified in the spleens of pregnant mice. High levels of suppressor cells have also been found in neonatal animals. The origin of these suppressor cells is unknown, but there appears to be a progressive increase in the mixed lymphocyte reaction from day one follwoing birth until day 21 when adult reactivity is approached. Studies on the ability of neonatal cells of various ages to present antigen were performed using cloned alloreactive and antigen-specific T cells. Neonatal animals also showed a defect in ability to reject tumors and to produce tumor necrotic factor following the injection of LPS. Whether this is secondary to quantitative or qualitative deficiency in macrophage function in the newborn is unknown. Some if not all of the defects in the neonate may be produced by soluble circulating suppressive substances which have been found in both amniotic fluid and neonate sera. Evidence is available that alpha-fetoprotein isolated from these sources is immunosuppressive and affects macrophage accessory function and inhibits the ability of macrophages to present antigen. Whether alpha-fetoprotein acts similarly in vivo has not been proven.